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A Novel Mutation in St14 at a Functionally Significant Amino Acid Residue Expands the Spectrum of Ichthyosis-Hypotrichosis Syndrome Publisher Pubmed



Youssefian L1, 2 ; Touati A1, 3 ; Saeidian AH1 ; Zargari O4 ; Zeinali S5, 6 ; Vahidnezhad H1, 5 ; Uitto J1
Authors
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Authors Affiliations
  1. 1. Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University, 233 S. 10th Street, Philadelphia, 19107, PA, United States
  2. 2. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Drexel University, College of Medicine, Philadelphia, PA, United States
  4. 4. Dana Clinic, Rasht, Iran
  5. 5. Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
  6. 6. Kawsar Human Genetics Research Center, Tehran, Iran

Source: Orphanet Journal of Rare Diseases Published:2017


Abstract

Background: Mutations in the ST14 gene, encoding the serine protease matriptase, have been associated with ichthyosis-hypotrichosis syndrome (IHS), a Mendelian disorder with skin and hair manifestations which include, in addition to ichthyosis and hypotrichosis, hypohidrosis and follicular atrophoderma. However, the understanding of the specific consequences of mutations in ST14 on the development of this syndrome is incomplete. Results: Using a targeted next-generation sequencing array of 38 ichthyosis-associated genes on a large cohort of 180 ichthyosis patients from a primarily consanguineous background, a previously unreported homozygous p.Asp482Asn mutation in ST14 was identified in a patient with IHS. This mutation affects an essential site within a ligand-binding domain of matriptase. Comparison with previous reports of IHS allowed further delineation of the phenotype of IHS in correlation with mutations present in these patients. Histological and ultrastructural analysis of skin and hair identified novel features in this disorder. Conclusions: This study correlates genotypic and phenotypic features of the rare disorder, IHS, expands the spectrum of pathology associated with the disorder, and provides clinical evidence of the importance of the Asp482 amino acid, previously shown to have an essential role in matriptase activation. © 2017 The Author(s).